Beta 2-adrenergic receptor activation enhances neurogenesis in Alzheimer's disease mice  

作　　者：Gao-shang Chai Yang-yang Wang Amina Yasheng Peng Zhao 

机构地区：[1]Department of Basic Medicine, Wuxi Medical School, Jiangnan University

出　　处：《Neural Regeneration Research》2016年第10期1617-1624,共8页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81601121,31500968;the Natural Science Foundation of Jiangsu Province of China,No.BK20150163;the Fundamental Research Fund for the Central Universities of China,No.JUSRP11567

摘　　要：Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer＇s disease. Enhancing adult hippocampal neuro- genesis has been pursued as a potential therapeutic strategy for Alzheimer＇s disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer＇s disease. To test this hypothe- sis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 （APP/PS1） mice using the agonist clenbuterol （intraperitoneal injection, 2 mg/kg）. We found that β2-adrenoceptor ac- tivation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines, lhese effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS 1 mice.Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer＇s disease. Enhancing adult hippocampal neuro- genesis has been pursued as a potential therapeutic strategy for Alzheimer＇s disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer＇s disease. To test this hypothe- sis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 （APP/PS1） mice using the agonist clenbuterol （intraperitoneal injection, 2 mg/kg）. We found that β2-adrenoceptor ac- tivation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines, lhese effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS 1 mice.

关 键 词：nerve regeneration Alzheimer＇s disease β2-adrenoceptors amyloid β NEUROGENESIS CLENBUTEROL APP/PS1 mice memory dendriticspine synapsin I SYNAPTOPHYSIN postsynaptic density 95 neural regeneration 

分 类 号：R749.16[医药卫生—神经病学与精神病学]